Anticevic Alan, Hu Sien, Zhang Sheng, Savic Aleksandar, Billingslea Eileen, Wasylink Suzanne, Repovs Grega, Cole Michael W, Bednarski Sarah, Krystal John H, Bloch Michael H, Li Chiang-Shan R, Pittenger Christopher
Department of Psychiatry, Yale University; Abraham Ribicoff Research Facilities, Yale University; NIAAA Center for the Translational Neuroscience of Alcoholism, Yale University.
Department of Psychiatry, Yale University.
Biol Psychiatry. 2014 Apr 15;75(8):595-605. doi: 10.1016/j.biopsych.2013.10.021. Epub 2013 Nov 4.
Obsessive-compulsive disorder (OCD) is associated with regional hyperactivity in cortico-striatal circuits. However, the large-scale patterns of abnormal neural connectivity remain uncharacterized. Resting-state functional connectivity studies have shown altered connectivity within the implicated circuitry, but they have used seed-driven approaches wherein a circuit of interest is defined a priori. This limits their ability to identify network abnormalities beyond the prevailing framework. This limitation is particularly problematic within the prefrontal cortex (PFC), which is large and heterogeneous and where a priori specification of seeds is therefore difficult. A hypothesis-neutral, data-driven approach to the analysis of connectivity is vital.
We analyzed resting-state functional connectivity data collected at 3T in 27 OCD patients and 66 matched control subjects with a recently developed data-driven global brain connectivity (GBC) method, both within the PFC and across the whole brain.
We found clusters of decreased connectivity in the left lateral PFC in both whole-brain and PFC-restricted analyses. Increased GBC was found in the right putamen and left cerebellar cortex. Within regions of interest in the basal ganglia and thalamus, we identified increased GBC in dorsal striatum and anterior thalamus, which was reduced in patients on medication. The ventral striatum/nucleus accumbens exhibited decreased global connectivity but increased connectivity specifically with the ventral anterior cingulate cortex in subjects with OCD.
These findings identify previously uncharacterized PFC and basal ganglia dysconnectivity in OCD and reveal differentially altered GBC in dorsal and ventral striatum. Results highlight complex disturbances in PFC networks, which could contribute to disrupted cortical-striatal-cerebellar circuits in OCD.
强迫症（OCD）与皮质-纹状体回路的局部过度活跃有关。然而，异常神经连接的大规模模式仍未明确。静息态功能连接研究显示，相关回路内的连接发生了改变，但这些研究采用的是种子驱动方法，即预先定义感兴趣的回路。这限制了它们识别现有框架之外网络异常的能力。在额叶前皮质（PFC）中，这种限制尤其成问题，因为额叶前皮质体积大且异质性强，因此很难预先指定种子。采用一种无假设、数据驱动的方法来分析连接性至关重要。
我们使用最近开发的数据驱动全脑连接（GBC）方法，分析了27名强迫症患者和66名匹配对照受试者在3T下采集的静息态功能连接数据，分析范围包括额叶前皮质内部和整个大脑。
在全脑和额叶前皮质受限分析中，我们发现左侧外侧额叶前皮质存在连接性降低的簇。右侧壳核和左侧小脑皮质的全脑连接性增加。在基底神经节和丘脑的感兴趣区域内，我们发现背侧纹状体和丘脑前核的全脑连接性增加，而药物治疗的患者中这种增加有所减少。强迫症患者的腹侧纹状体/伏隔核整体连接性降低，但与腹侧前扣带回皮质的连接性增加。
这些发现确定了强迫症中以前未明确的额叶前皮质和基底神经节连接障碍，并揭示了背侧和腹侧纹状体中全脑连接性的差异改变。结果突出了额叶前皮质网络中的复杂紊乱，这可能导致强迫症中皮质-纹状体-小脑回路的破坏。
